CLINICAL BIOCHEMISTRY & METABOLIC MEDICINE
EIGHTH EDITION
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
CLINICAL BIOCHEMISTRY & METABOLIC MEDICINE
EIGHTH EDITION
Professor Martin Andrew Crook BSc MB BS MA PhD FRCPath FRCPI FRCPConsultant in Chemical Pathology and Metabolic MedicineGuy’s, St Thomas’ and University Hospital Lewisham, London, UK, and Visiting Professor, School of Science, University of Greenwich, UK
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
First published in Great Britain in 1971 by Lloyd-Luke (Medical Books) LtdSecond edition 1975Third edition 1979Fourth edition 1984Fifth edition published in 1988 by Edward Arnold (Publishers) LtdSixth edition published in 1994Seventh edition published in 2006 by Hodder ArnoldThis eighth edition published in 2012 by Hodder Arnold, an imprint of Hodder Education, Hodder and Stoughton Ltd, a division of Hachette UK,338 Euston Road, London, NW1 3BH
http://www.hodderarnold.com
© 2012 Hodder & Stoughton Ltd
All rights reserved. Apart from any use permitted under UK copyright law, this publication may only be reproduced, stored or transmitted in any form or by any means with prior permission in writing of the publishers or in the case of reprographic production in accordance with the terms of licences issued by the Copyright Licensing Agency. In the United Kingdom such licences are issued by the Copyright Licensing Agency: Saffron House, 6–10 Kirby Street, London EC1N 8TS.
Whilst the advice and information in this book are believed to be true and accurate at the date of going to press, neither the author nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. In particular (but without limiting the generality of the preceding disclaimer), every effort has been made to check drug dosages; however, it is still possible that errors have been missed. Furthermore, dosage schedules are constantly being revised and new side effects recognized. For these reasons the reader is strongly urged to consult the drug companies’ printed instructions, and their websites, before administering any of the drugs recommended in this book.
British Library Cataloguing in Publication DataA catalogue record for this book is available from the British Library
Library of Congress Cataloging-in-Publication DataA catalog record for this book is available from the Library of Congress
ISBN-13 978-1-4441-4414-7ISBN-13 [ISE] 978-1-4441-4416-1
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
Contents
Preface vii
List of abbreviations viii
1 Requesting laboratory tests and interpreting the results 1
2 Water and sodium 6
3 The kidneys 36
4 Acid–base disturbances 59
5 Potassium 83
6 Calcium, phosphate and magnesium 95
7 The hypothalamus and pituitary gland 116
8 The adrenal cortex 129
9 The reproductive system 146
10 Pregnancy and infertility 157
11 Thyroid function 164
12 Carbohydrate metabolism 176
13 Plasma lipids and lipoproteins 200
14 Nutrition 216
15 Vitamins, trace elements and metals 224
16 The gastrointestinal tract 235
17 Liver disorders and gallstones 252
18 Plasma enzymes in diagnosis (clinical enzymology) 270
19 Proteins in plasma and urine 282
20 Purine and urate metabolism 303
21 Disorders of haem metabolism: iron and the porphyrias 310
22 Cardiovascular disease 325
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
Contentsvi
23 Cerebrospinal, pleural and ascitic fl uids 332
24 Metabolic effects of tumours 338
25 Therapeutic drug monitoring and poisoning 347
26 Clinical biochemistry at the extremes of age 358
27 Inborn errors of metabolism 371
28 Genetics and deoxyribonucleic acid-based technology in clinical biochemistry 384
29 Patient sample collection and use of the laboratory 391
30 Point-of-care testing 397
Appendix 1: Units in clinical chemistry 401
Index 403
COMPANION WEBSITE
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www.hodderplus.com/clinicalbiochemistry
The website contains downloadable images from the book as well as self assessment questions.
To access these resources please register on the website using the following access details:
Serial number: 145jw76mc8fw
Once you have registered you will not need the serial number but can log in using the username and password that you will create during your registration.
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
Were it not for the textbook Clinical Chemistry in Diagnosis and Treatment by Joan Zilva and Peter Pannall, I would not be a chemical pathologist. As a medical student, I was so struck by its clarity, depth and clinical relevance that I decided that theirs was the medical field I wished to work in.
Over the years, the fi eld of clinical biochemistry has changed radically. Confusingly, there is no consensus on the name for this fi eld of medicine, which is known variously as clinical chemistry, chemical pathology or clinical biochemistry, to name but a few. Additionally, the fi eld now overlaps with that of metabolic medicine, a clinical specialty involved with the management and treatment of patients with disorders of metabolism. Clinical biochemistry laboratories have become further automated, molecular biology technologies have entered the diagnostic arena, and chemical pathologists have become more clinically orientated towards running out-patient clinics for a variety of biochemical disturbances. This book aims to address these new changes. Indeed, it is diffi cult to imagine a branch of medicine that does not at some time require clinical biochemistry tests, which may not be too surprising, given the fact that every body cell is composed of chemicals!
Unfortunately, there have been some diffi culties in recent times, with a relative shortage of graduates entering the specialty, which has not been helped by some people’s attitude that clinical biochemistry is merely a laboratory factory churning out results that anyone can interpret. There are also concerns that medical student clinical biochemistry teaching may become ‘diluted’ as part of an expanding curriculum. It is hoped that this book will excite a new generation to enter this fascinating and essential fi eld, as well as benefi t patients as their doctors learn more about their biochemical and metabolic problems.
I am most grateful to Dr Sethsiri Wijeratne, Dr Alam Garrib (particularly for molecular biology expertise) and Dr Paul Eldridge for constructive criticism of the text. I am also grateful to Professor Philip Mayne for his earlier contributions and the anonymous medical student reviewer(s) who commented on the text. The book has also greatly benefi ted from the wise, helpful and experienced input of Dr Andrew Day – many thanks. Although every effort has been made to avoid inaccuracies and errors, it is almost inevitable that some may still be present, and feedback from readers is therefore welcome.
Martin CrookLondon, 2012
Preface
Disclaimer The publishers and author accept no responsibility for errors in the text or misuse of the material presented. Drugs and their doses should be checked with a pharmacy, and the investigation protocols with an appropriate clinical laboratory. Dynamic test protocols should be checked with an accredited clinical investigation unit and may require different instructions in the elderly, children and the obese.
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
ABC1 adenosine triphosphate-binding cassette protein 1
ACE angiotensin-converting enzymeACP acid phosphataseACR albumin to creatinine ratioACTH adrenocorticotrophic hormone
(corticotrophin)ADH antidiuretic hormone (arginine
vasopressin)A&E accident and emergency (department)AFP a-fetoproteinAIDS acquired immunodeficiency syndromeAIS autoimmune insulin syndromeAKI acute kidney injuryALA 5-aminolaevulinic acidALP alkaline phosphataseALT alanine aminotransferase (also known
as glutamate pyruvate aminotransferase, GPT)
AMC arm muscle circumferenceANA antinuclear antibodyANCA antineutrophil cytoplasmic antibodyANP atrial natriuretic peptideAPA aldosterone-producing adenomaapo apolipoproteinAPRT adenine phosphoribosyl transferaseAPUD amine precursor uptake and
decarboxylationARA angiotensin II receptor antagonistARB angiotensin II receptor blockerARMS amplification refractory mutation
systemAST aspartate aminotransferase (also
known as glutamate oxaloacetate aminotransferase, GOT)
ATPase adenosine triphosphataseATP adenosine triphosphate
BJP Bence Jones proteinBMD bone mineral densityBMI body mass indexBMR basal metabolic rateBNP brain natriuretic peptideBPH benign prostatic hyperplasia
CA carbohydrate antigenCaE calcium excreted per litre of glomerular
filtrateCAH congenital adrenal hyperplasiacAMP cyclic adenosine monophosphateCaSR calcium-sensing receptorCAT computerized axial tomographyCBG cortisol-binding globulin (transcortin)CD carbonate dehydratase (carbonic
anhydrase)CEA carcinoembryonic antigenCETP cholesterol ester transfer proteinCK creatine kinaseCKD chronic kidney diseaseCNP C-type natriuretic peptideCNS central nervous systemCoA coenzyme ACOPD chronic obstructive pulmonary diseaseCRH corticotrophin-releasing hormoneCRP C-reactive proteinCSF cerebrospinal fluidCT computerized tomographyCV coefficient of variationCys C cystatin C
2,3-DPG 2,3-diphosphoglycerateDDAVP 1-desamino-8-D-arginine vasopressin
(desmopressin acetate)DHEA dehydroepiandrosteroneDHEAS dehydroepiandrosterone sulphateDIT di-iodotyrosineDNA deoxyribonucleic acidDPP-4 dipeptidyl peptidase-4DVT deep vein thrombosis
ECF extracellular fluidECG electrocardiogramEDTA ethylenediamine tetra-acetic acideGFR estimated glomerular filtration rateENA extractable nuclear antigenENT ear, nose and throat (department)ERCP endoscopic retrograde
cholangiopancreatographyESR erythrocyte sedimentation rate
List of abbreviations
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
List of abbreviations ix
EUS endoscopic ultrasonography
FAD flavine adenine dinucleotideFCH familial combined hyperlipidaemiaFDH familial dysalbuminaemic
hyperthyroxinaemiaFENa% fractional excretion of sodiumFEPi% fractional excretion of phosphateFH familial hypercholesterolaemiaFMN flavine mononucleotideFSH follicle-stimulating hormonefT
4 free T
4
fT3 free T
3
GAD glutamic decarboxylaseGDM gestational diabetes mellitusGFR glomerular filtration rateGGT g-glutamyl transferaseGH growth hormoneGHRH growth hormone-releasing hormoneGIP gastric inhibitory peptideGLP-1 glucagon-like peptide 1GnRH gonadotrophin-releasing hormoneG6P glucose-6-phosphateG6PD glucose-6-phosphate dehydrogenaseGRA glucocorticoid remediable aldosteronism
HAV hepatitis A virusHb haemoglobinHbA
1c glycated haemoglobin
HBsAg viral surface antigen
HBD hydroxybutyrate dehydrogenaseHBV hepatitis B virushCG human chorionic gonadotrophinHCV hepatitis C virusHDL high-density lipoproteinHELP heparin extracorporeal low-density
lipoprotein precipitationHFE human haemochromatosis proteinHGPRT hypoxanthine–guanine phosphoribosyl
transferase5-HIAA 5-hydroxyindole acetic acidHIV human immunodeficiency virusHLA human leucocyte antigenHMG-CoA 3-hydroxy-3-methyl glutaryl coenzyme AHMMA 4-hydroxy-3-methoxymandelic acidHNF hepatocyte nuclear factorHONK hyperosmolal non-ketotic (coma)HRT hormone replacement therapyhs-CRP high-sensitivity C-reactive protein
5-HT hydroxytryptamine (serotonin)5-HTP hydroxytryptophanHVA homovanillic acid
IAH idiopathic adrenal hyperplasiaIDL intermediate-density lipoproteinIDMS isotope dilution mass spectrometryIEM inborn errors of metabolismIFG impaired fasting glucoseIFN interferonIg immunoglobulinIGF insulin-like growth factorIGT impaired glucose toleranceIL interleukinINR international normalized ratio
LADA latent autoimmune diabetes of adultsLCAT lecithin–cholesterol acyltransferaseLDH lactate dehydrogenaseLDL low-density lipoproteinLH luteinizing hormoneLR likelihood ratio
MCADD medium-chain acyl coenzyme A dehydrogenase deficiency
MCH mean corpuscular haemoglobinMCV mean corpuscular volumeMDRD modification of diet in renal disease
(formula)MEGX monoethylglycinexylidideMEN multiple endocrine neoplasiaMGUS monoclonal gammopathy of
undetermined significanceMIBG metaiodobenzylguanidineMIT mono-iodotyrosineMODY maturity-onset diabetes of the youngMPS mucopolysaccharidosisMRCP magnetic resonance
cholangiopancreatographyMRI magnetic resonance imagingmRNA messenger ribonucleic acidMSH melanocyte-stimulating hormonemtDNA mitochondrial DNAMTHFR methylenetetrahydrofolate reductase
NAD nicotinamide adenine dinucleotideNADP nicotinamide adenine dinucleotide
phosphateNAFLD non-alcoholic fatty liver diseaseNAG N-acetyl-b-D-glucosaminidase
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education
List of abbreviationsx
NASH non-alcoholic steatotic hepatitisNEFA non-esterified fatty acidNGAL neutrophil gelatinase-associated lipocalinNHS National Health ServiceNICTH non-islet cell tumour hypoglycaemiaNP natriuretic peptideNSAID non-steroidal anti-inflammatory drugNSTEMI non-ST segment elevation myocardial
infarction
OGTT oral glucose tolerance testOTC ornithine transcarbamylase
PABA para-amino benzoic acidPBG porphobilinogenPCR polymerase chain reactionPEG polyethylene glycolPH primary hyperaldosteronismPI protease inhibitorPIVKA proteins induced by vitamin K absencePKU phenylketonuriaPNI prognostic nutritional indexPOCT point-of-care testingPPAR peroxisome proliferator-activated receptorPRPP phosphoribosyl pyrophosphatePSA prostate-specific antigenPTH parathyroid hormonePTHRP parathyroid hormone-related protein
RBP retinol-binding proteinRDS respiratory distress syndromeRFLP restriction fragment length
polymorphismRNA ribonucleic acidROC receiver operating characteristic (curve)RRT renal replacement therapy
SCID severe combined immunodeficiencySD standard deviationSHBG sex-hormone-binding globulinSIADH syndrome of inappropriate antidiuretic
hormone secretionSLE systemic lupus erythematosusSTEMI ST-segment elevation myocardial
infarction
T3 tri-iodothyronine
T4 thyroxine
TBG thyroxine-binding globulinTBW total body waterTCA tricarboxylic acidTfR transferrin receptorTIBC total iron-binding capacityTNF tumour necrosis factorTPO thyroid peroxidaseTPMT thiopurine methyltransferaseTRH thyrotrophin-releasing hormoneTSH thyroid-stimulating hormoneTSI thyroid-stimulating immunoglobulinTTKG transtubular potassium gradient
UGT uridine glucuronyl transferaseUIBC unsaturated iron-binding capacityURL upper reference limit
VIP vasoactive intestinal polypeptideVLCFA very long-chain fatty acidVLDL very low-density lipoproteinVDBP vitamin D-binding proteinVDR vitamin D receptor
WHO World Health Organizati on
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Clinical Biochemistry and Metabolic Medicine © 2012 Martin A. Crook / Hodder Education